欢迎来到《四川大学学报(医学版)》

骨质疏松症伴阻塞性睡眠呼吸暂停综合征患者血清蛋白组学分析

Proteomic Analysis of Bone Serum Protein in Patients With Osteoporosis Accompanied by Obstructive Sleep Apnea Syndrome

  • 摘要:
    目的 通过蛋白组学技术进行伴有阻塞性睡眠呼吸暂停综合征(OSAS)的骨质疏松症与单纯骨质疏松症患者骨血清蛋白差异分析。
    方法 选择2022年6月–2024年6月于我院就诊的80例骨质疏松症患者为研究对象,据多导睡眠监测结果分为OSAS-骨质疏松症组(n=42)与单纯骨质疏松症组(n=38)。采用倾向性匹配将各协变量纳入logistic模型中进行匹配,使两组患者的个体特征基本平衡,最终成功匹配了20对,采用匹配后的样本进行后续分析。利用电离质谱获得质谱图。利用主成分分析(PCA)对数据分析不同组别的代谢模式差异。应用偏最小二乘判别分析(PLS-DA)进一步进行数据分析。利用正交偏最小二乘判别分析(OPLS-DA)方法对样本数据进行分析。利用OPLS-DA计算各物质的VIP值,进行组间差异代谢物质的筛选。利用热图显示OSAS-骨质疏松症组与单纯骨质疏松症组代谢谱的差异。对差异代谢物进行富集通路分析。
    结果 倾向性匹配后两组患者的个体特征基本平衡。质谱图显示OSAS-骨质疏松症组与单纯骨质疏松症组表现出明显差异。PCA得分图中,两组分离趋势不显著。PLS-DA得分图可见分离趋势,R2Q2均小于真实模型,模型可信。OPLS-DA的总R2X=0.635,R2Y=0.879,O2Y=0.728,两组分离趋势明显。筛选出两组差异代谢物包括硬脂酰油酰甘油磷酸胆碱、磷酸胆碱、L-组氨酸、芥酸酰胺、2'-脱氧尿苷、1-棕榈酰甘油、胸腺嘧啶、酪胺、L-焦谷氨酸、L-谷氨酸、肉豆蔻酸、甘油-3-磷酸、辛酸、孕烯醇酮、L-精氨酸、D-4-羟基苯甘氨酸、异丁酸17种物质。热图显示,OSAS-骨质疏松症组与单纯骨质疏松症组患者代谢谱差异具有统计学意义。富集通路分析结果显示涉及27条代谢通路,以 P<0.05,Pathway Impact>0.2 为条件,筛选出最具有意义的三条代谢途径,主要为丙氨酸、天冬氨酸和谷氨酸代谢、精氨酸生物合成、组氨酸代谢等途径。
    结论 OSAS-骨质疏松症组与单纯骨质疏松症组代谢谱有显著差异。

     

    Abstract:
    Objective To analyze the differences in bone serum protein between patients with osteoporosis accompanied by obstructive sleep apnea syndrome (OSAS) and those with osteoporosis only using proteomics.
    Methods A total of 80 osteoporosis patients who attended our hospital between June 2022 and June 2024 were enrolled. Based on their polysomnography results, the participants were divided into an OSAS and osteoporosis comorbidity (OSAS-osteoporosis) group (n = 42) and an osteoporosis only group (n = 38). Propensity score matching was applied to incorporate covariates in logistic regression so that the individual characteristics of the two groups of patients were generally balanced. Following the matching procedure, a final cohort of 20 matched pairs was obtained and subsequently utilized for further analysis. The mass spectrum was obtained using laser desorption ionization mass spectrometry. Principal component analysis (PCA) was performed to assess differences in metabolic patterns between groups. Partial least squares discriminant analysis (PLS-DA) and orthogonal PLS-DA (OPLS-DA) were employed for further data analysis. Variable importance in projection (VIP) scores of each substance were calculated with OPLS-DA to screen the metabolites showing inter-group differences. Heatmaps were generated to visualize metabolic profile differences between the OSAS-osteoporosis group and the osteoporosis group. Enrichment pathway analysis was conducted on the differential identified metabolites.
    Results After propensity score matching, individual characteristics between the groups were well balanced. Mass spectrometry revealed significant differences between the OSAS-osteoporosis and osteoporosis groups. In the PCA score plot, the separation trend of the two groups was not significant. The PLS-DA score plot showed a discernible separation trend, with R2 and Q2 lower than those of the corresponding results of the real model, confirming the reliability of the model. OPLS-DA showed that the total R2X of the model was 0.635, R2Y was 0.879, and O2Y was 0.728, showing obvious separation trends between the two groups. A total of 16 differential metabolites were identified, including stearyl-oleyl-glycerol phosphate choline, phosphate choline, L-histidine, erucamide, 2'-deoxyuridine, 1-palmitoyl glycerol, thymine, tyramine, L-pyroglutamic acid, L-glutamic acid, myristate, glycerol-3-phosphate, caprylic acid, pregnenolone, L-arginine, D-4-hydroxyphenylglycine, and isobutyric acid. Heatmaps showed significant differences in metabolic profiles between the OSAS-osteoporosis group and the osteoporosis group. Pathway enrichment analysis showed that 27 metabolic pathways were involved. 27 metabolic pathways. Under the conditions of P < 0.05 and pathway impact > 0.2, the three most significant metabolic pathways identified included mainly alanine, aspartate, and glutamate metabolism, arginine biosynthesis, and histidine metabolism.
    Conclusion Significant differences were observed in the metabolic profiles between patients with both OSAS and osteoporosis and those with osteoporosis alone.

     

/

返回文章
返回